Influence of the Temperature on Coccolith-Containing Systems from Emiliania huxleyi Cultivations

Thermogravimetric analysis of a coccolith-containing biogenic broth showed a three-step degradation process. According to this system behavior, the biogenic broth was heated to specific temperatures and characterized in terms of its morphology, surface chemistry, and crystallinity. The elemental and organic composition of the treated samples was also evaluated and compared to the reference material. The presented results were acquired in an effort to exploit pretreatment scenarios for such a biogenic system that would improve and support a separation process.     

Recycling von marinen Sekundärrohstoffen

As a waste product, oyster shells pose a major environmental pollution problem and the reuse of the material is becoming increasingly important. Since the comminution process in the recycling of secondary raw materials defines the properties of the material, oyster shells were grinded using a planetary ball mill and an impact mill and the fractions obtained were analyzed in terms of size and shape and compared with each other. A comminuted material from the impact mill was used for a series of wetting experiments, which helped to demonstrate the surface free energy of the material.     

Archetypal personalities of software engineers and their work preferences: a new perspective for empirical studies

As the area of Software Engineering (SE) matures the role of human factors in software development is commonly recognized as important. Increasingly we see empirical studies that investigate the connection between, for example, personalities and preferences, attitudes or performances of software engineers. Statistical analysis holds a key role by providing the means for uncovering associations between various facets of human factors and behavioral effects on projects and outcomes. Traditional statistical techniques tend to explore and interpret the multidimensional personality and behavioral data from an “average-point” perspective, targeting central trends. This paper introduces a methodology with statistical tools that can provide a new and different perspective for this type of SE data. It seeks the boundaries of a psychometric dataset and discovers reference or “benchmark” personalities, the archetypal personalities. Then, the method examines the placement of all individuals in the dataset in relation to the archetypes. Furthermore, the SE preference characteristics, or generally, any other types of behavioral SE data, are analyzed with respect to the archetypes. As a case to exemplify the methodology we analyze personality and project preference data from 276 master level SE students and compare to previous “average-point” statistical analysis of the same data. We also discuss how Archetypal Analysis, the heart of the proposed methodology, combined with multi-correspondence analysis might be of general use in empirical SE.     

Tissue-Specific Methylation Biosignatures for Monitoring Diseases: An In Silico Approach

Tissue-specific gene methylation events are key to the pathogenesis of several diseases and can be utilized for diagnosis and monitoring. Here, we established an in silico pipeline to analyze high-throughput methylome datasets to identify specific methylation fingerprints in three pathological entities of major burden, i.e., breast cancer (BrCa), osteoarthritis (OA) and diabetes mellitus (DM). Differential methylation analysis was conducted to compare tissues/cells related to the pathology and different types of healthy tissues, revealing Differentially Methylated Genes (DMGs). Highly performing and low feature number biosignatures were built with automated machine learning, including: (1) a five-gene biosignature discriminating BrCa tissue from healthy tissues (AUC 0.987 and precision 0.987), (2) three equivalent OA cartilage-specific biosignatures containing four genes each (AUC 0.978 and precision 0.986) and (3) a four-gene pancreatic β-cell-specific biosignature (AUC 0.984 and precision 0.995). Next, the BrCa biosignature was validated using an independent ccfDNA dataset showing an AUC and precision of 1.000, verifying the biosignature’s applicability in liquid biopsy. Functional and protein interaction prediction analysis revealed that most DMGs identified are involved in pathways known to be related to the studied diseases or pointed to new ones. Overall, our data-driven approach contributes to the maximum exploitation of high-throughput methylome readings, helping to establish specific disease profiles to be applied in clinical practice and to understand human pathology.     

Selective Binding of Small Molecules to Vibrio cholerae DsbA Offers a Starting Point for the Design of Novel Antibacterials

DsbA enzymes catalyze oxidative folding of proteins that are secreted into the periplasm of Gram-negative bacteria, and they are indispensable for the virulence of human pathogens such as Vibrio cholerae and Escherichia coli. Therefore, targeting DsbA represents an attractive approach to control bacterial virulence. X-ray crystal structures reveal that DsbA enzymes share a similar fold, however, the hydrophobic groove adjacent to the active site, which is implicated in substrate binding, is shorter and flatter in the structure of V. cholerae DsbA (VcDsbA) compared to E. coli DsbA (EcDsbA). The flat and largely featureless nature of this hydrophobic groove is challenging for the development of small molecule inhibitors. Using fragment-based screening approaches, we have identified a novel small molecule, based on the benzimidazole scaffold, that binds to the hydrophobic groove of oxidized VcDsbA with a K_D of 446±10 μM. The same benzimidazole compound has ∼8-fold selectivity for VcDsbA over EcDsbA and binds to oxidized EcDsbA, with K_D>3.5 mM. We generated a model of the benzimidazole complex with VcDsbA using NMR data but were unable to determine the structure of the benzimidazole bound EcDsbA using either NMR or X-ray crystallography. Therefore, a structural basis for the observed selectivity is unclear. To better understand ligand binding to these two enzymes we crystallized each of them in complex with a known ligand, the bile salt sodium taurocholate. The crystal structures show that taurocholate adopts different binding poses in complex with VcDsbA and EcDsbA, and reveal the protein-ligand interactions that stabilize the different modes of binding. This work highlights the capacity of fragment-based drug discovery to identify inhibitors of challenging protein targets. In addition, it provides a starting point for development of more potent and specific VcDsbA inhibitors that act through a novel anti-virulence mechanism.